C-5 Substituted heteroaryl 3-pyridinecarbonitriles as PKC[theta] inhibitors: Part I

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 18; pp. 5423 - 5425
• Main Authors: Subrath, Joan, Wang, Daniel, Wu, Biqi, Niu, Chuansheng, Boschelli, Diane H, Lee, Julie, Yang, Xiaoke, Brennan, Agnes, Chaudhary, Divya
• Format: Journal Article
• Language: English
• Published: 15.09.2009
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2009.07.109

We earlier reported that 3-pyridinecarbonitriiles with a 4-methylindolyl-5-amino group at C-4 and a phenyl group at C-5 were inhibitors of PKC[theta]. Keeping the group at C-4 of the pyridine core constant, we varied the water solubilizing group on the phenyl ring at C-5 and then replaced the C-5 phenyl ring with several monocyclic heteroaryl rings, including furan, thiophene and pyridine. Analog 6e with a 4- methylindol-5-ylamino group at C-4 and a 5-[(4-methylpiperazin-1-yl)methyl]-2-furyl group C-5 had an IC sub(50) value of 4.5 nM for the inhibition of PKC[theta].